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      To exploit the tumor microenvironment: Since the EPR effect fails in the clinic, what is the future of nanomedicine?

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          Abstract

          Tumor targeting by nanomedicine-based therapeutics has emerged as a promising approach to overcome the lack of specificity of conventional chemotherapeutic agents and to provide clinicians the ability to overcome shortcomings of current cancer treatment. The major underlying mechanism of the design of nanomedicines was the Enhanced Permeability and Retention (EPR) effect, considered as the "royal gate" in the drug delivery field. However, after the publication of thousands of research papers, the verdict has been handed down: the EPR effect works in rodents but not in humans! Thus the basic rationale of the design and development of nanomedicines in cancer therapy is failing making it necessary to stop claiming efficacy gains via the EPR effect, while tumor targeting cannot be proved in the clinic. It is probably time to dethrone the EPR effect and to ask the question: what is the future of nanomedicines without the EPR effect? The aim of this review is to provide a general overview on (i) the current state of the EPR effect, (ii) the future of nanomedicine and (iii) the strategies of modulation of the tumor microenvironment to improve the delivery of nanomedicine.

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          Author and article information

          Journal
          J Control Release
          Journal of controlled release : official journal of the Controlled Release Society
          Elsevier BV
          1873-4995
          0168-3659
          Dec 28 2016
          : 244
          : Pt A
          Affiliations
          [1 ] Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier, 73 bte B1 73.12, 1200 Brussels, Belgium. Electronic address: fabienne.danhier@uclouvain.be.
          Article
          S0168-3659(16)30779-9
          10.1016/j.jconrel.2016.11.015
          27871992
          708d283a-b708-49a7-8b43-de2e5aea5886
          History

          Cancer,Drug delivery,EPR effect,Nanomedicine,Tumor targeting

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